Magnetic Sorter Channels for Stem Cells

干细胞磁力分选通道

• 批准号: 7127227
• 负责人: PAUL W TODD
• 金额: $ 31.33万
• 依托单位: TECHSHOT, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-29 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127227
• 关键词: biomedical equipment development; blood treatment; bone marrow; cell sorting; clinical biomedical equipment; consumable /disposable biomedical equipment; cord blood; hematopoietic stem cells; human tissue; immunomagnetic separation

DESCRIPTION (provided by applicant): SHOT proposes research leading to the commercialization of technology for magnetic isolation of hematopoietic stem cells from human umbilical cord blood, bone marrow and peripheral apheresis product cells. Bone marrow transplantation (BMT) is an established therapy for certain leukemias and other hematologic diseases. The high cure potential of allogeneic BMT is limited by the need for matched histocompatible donors to minimize the possibility of graft-versus-host disease. The ability to isolate stem cells opens a new clinical approach for engineering a most suitable graft. In Phase I research SHOT'S collaborators at The Cleveland Clinic Foundation established that the Quadrupole Magnetic (flow) Sorter (QMS) fulfills most of the requirements for hematologic stem cell selection with its much higher yield and capacity relative to most other methods, and SHOT demonstrated the manufacture of prototype sterile disposable magnetic flow channels and a QMS system. Phase II research thus calls for the design of a package, consisting of an automated QMS facility and disposable channels with sufficient precision, reproducibility and capacity to qualify ultimately for the isolation of human hematopoietic stem cells in the clinical setting. SHOT will (1) perform research to increase the sample size that the QMS system can process from 140 ml to 500 ml; (2) investigate imumunomagnetic labeling technologies to increase the magnetic mobility of the labeled cells, thus increasing sample processing speed; (3) refine the QMS system design in accordance with Current Good Manufacturing Practices (cGMP) design guidelines to incorporate lessons learned, making the system faster, more versatile and more user-friendly; and (4) complete a betatesting program in nationally-known cancer and cell therapy laboratories. The proposed Phase II end items are two pre-market manufactured QMS system prototypes and a set of refined separation channels capable of supporting the beta testing program and ready for the cGMP verification process. SHOT'S goal for the QMS system is the capability of sorting 10 million cells/sec at a total throughput of 8 ml/min or greater with a recovery and purity of 60% or greater. Phase III activities will include manufacture of the QMS systems and separation channels for sale in the research market, as well as a directed effort towards FDA compliance for sales of the QMS systems and separation channels under cGMP in the clinical setting.

描述（由申请人提供）：SHOT提出了一项研究，旨在将从人脐带血、骨髓和外周血单采产物细胞中磁性分离造血干细胞的技术商业化。骨髓移植（BMT）是治疗某些白血病和其他血液病的一种既定疗法。异基因BMT的高治愈潜力受到需要匹配的组织相容性供体以最小化移植物抗宿主病的可能性的限制。分离干细胞的能力为设计最合适的移植物开辟了一种新的临床方法。在第一阶段研究中，SHOT在克利夫兰临床基金会的合作者确定，四极磁（流）分选机（QMS）满足血液干细胞选择的大部分要求，其产量和容量比大多数其他方法高得多，SHOT展示了原型无菌一次性磁流通道和QMS系统的制造。因此，II期研究需要设计一种包装，包括自动化QMS设施和一次性通道，具有足够的精度，再现性和能力，最终有资格在临床环境中分离人造血干细胞。SHOT将（1）进行研究，以将QMS系统可处理的样本量从140 ml增加到500 ml;（2）研究免疫磁性标记技术，以增加标记细胞的磁迁移率，从而提高样本处理速度;（3）根据现行良好生产规范（cGMP）设计指南，完善质量管理体系设计，以吸取经验教训，使系统更快、更通用和更用户友好;和（4）在全国知名的癌症和细胞治疗实验室完成β测试计划。拟定的第II阶段最终产品是两个上市前生产的QMS系统原型和一套能够支持beta测试程序并准备用于cGMP验证过程的精制分离通道。SHOT的QMS系统的目标是以8 ml/min或更高的总通量分选1000万个细胞/秒的能力，回收率和纯度为60%或更高。III期活动将包括生产用于研究市场销售的QMS系统和分离通道，以及在临床环境中根据cGMP销售QMS系统和分离通道以达到FDA合规性的直接努力。